The Philadelphia Breast Cancer Family Registry is a clinic-based family registry, one of six international collaborating Cancer Family Registry (CFR) sites sponsored by the National Cancer Institute (NCI). The overall objective is to maintain, enhance and exploit the research potential of the B-CFR for use by interdisciplinary teams of researchers. Led by Mary B. Daly, M.D., Ph.D., Director of Cancer Prevention and Control at the Fox Chase Cancer Center (FCCC), the Philadelphia B-CFR has focused its early efforts on recruiting families who met the eligibility criteria for familial/hereditary breast/ovarian cancer. Genotyping for BRCA1 and BRCA2 mutations has been performed through the Clinical Genetics Laboratory directed by Dr. Andrew Godwin. In collaboration with Dr. Generosa Grana at Cooper University Hospital in Camden, NJ, we also extended recruitment, genetic counseling and testing to a cohort of minority families. We focused on a thorough documentation and review of pathology samples from affected family members. A rich resource of blood and tumor specimens has been collected and stored at Coriell Cell Repositories under the direction of Dr. Jeanne Beck. As a result of these efforts, we have assembled a cohort of highly motivated families, well characterized in terms of family and medical history and risk factor exposures, for use by the international community to conduct research. As one of the three clinic-based sites, we are in a strong position to translate the findings of the scientific community to the clinical setting and to the families who have become our partners in this research. In the next funding period, we plan to build on these accomplishments with a focus on our research agenda and the strengthening of platforms to accomplish our next generation of goals. Our specific aims are to: continue to conduct targeted recruitment of early onset, minority and mutation carrier families;coordinate a thorough effort to obtain standardized follow-up data on all participants;enhance the value of the Biospecimen Repository with renewable cell lines and tissue microarrays;continue to take an active role in all of the B-CFR working groups and newly defined platforms, and most importantly, utilize the resources of the B-CFR to address important research questions about familial and non-familial breast cancer. The Philadelphia B-CFR will take the lead in developing the Behavioral and Survivorship Platform to facilitate research in these areas for both CFRs as well as outside investigators. Public Health Significance: The B-CFR sites have formed a research partnership with over 14,000 families to speed discovery in the prevention, early detection and treatment of familial breast cancer. Through our continued partnership, we hope to understand the pathways of breast cancer risk and ultimately reduce that risk for all women.